Hyperlipidemia – Causes, Symptoms, Treatment

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Hyperlipidemia is a condition that incorporates various genetic and acquired disorders that describe elevated lipid levels within the human body. Hyperlipidemia is extremely common, especially in the Western hemisphere, but also throughout the world. Alternatively, a more objective definition describes hyperlipidemia as low-density lipoprotein (LDL), total cholesterol, triglyceride levels, or lipoprotein levels greater than the 90th percentile in comparison to the general population, or an HDL level less than the 10th percentile when compared to the general population. Lipids typically include cholesterol levels, lipoproteins, chylomicrons, VLDL, LDL, apolipoproteins, and HDL.

Hyperlipidemia is abnormally elevated levels of any or all lipids or lipoproteins in the blood.[rx] Hyperlipidemia is an umbrella term that refers to acquired or genetic disorders that result in high levels of lipids (fats, cholesterol, or triglycerides) circulating in the blood.[rx] This disease is usually chronic and requires ongoing medication to control blood lipid levels.[rx] Lipids (water-insoluble molecules) are transported in a protein capsule.[rx] The size of that capsule, or lipoprotein, determines its density.[rx] The lipoprotein density and type of apolipoproteins it contains determines the fate of the particle and its influence on metabolism.

Types of Hyperlipidemia

Classification of hyperlipidemias as defined by the NCEP ATP 3. All concentrations are expressed as mg/dL

LDL Cholesterol
<100 Optimal
100 – 129 Near or above optimal
130 – 159 Borderline high
160 – 189 High
≥ 190 Very high
Total Cholesterol
<200 Desirable
200 – 239 Borderline high
≥ 240 High
HDL Cholesterol*
<40 Low
≥ 60 High
<150 Normal
150 – 199 Borderline high
200 – 499 High
≥ 500 Very high

Type I

Type I hyperlipoproteinemia exists in several forms:

  • Lipoprotein lipase deficiency (type Ia), due to a deficiency of lipoprotein lipase (LPL) or altered apolipoprotein C2, resulting in elevated chylomicrons, the particles that transfer fatty acids from the digestive tract to the liver
  • Familial apoprotein CII deficiency (type Ib),[rx][rx] a condition caused by a lack of lipoprotein lipase activator.[rx]
  • Chylomicronemia due to circulating inhibitor of lipoprotein lipase (type Ic)[rx]

Type I hyperlipoproteinemia usually presents in childhood with eruptive xanthomata and abdominal colic. Complications include retinal vein occlusion, acute pancreatitis, steatosis, and organomegaly, and lipemia retinalis.

Type II

Hyperlipoproteinemia type II, by far the most common form, is further classified into types IIa and IIb, depending mainly on whether elevation in the triglyceride level occurs in addition to LDL cholesterol.

Type IIa

This may be sporadic (due to dietary factors), polygenic, or truly familial as a result of a mutation either in the LDL receptor gene on chromosome 19 (0.2% of the population) or the ApoB gene (0.2%). The familial form is characterized by tendon xanthoma, xanthelasma, and premature cardiovascular disease. The incidence of this disease is about one in 500 for heterozygotes, and one in 1,000,000 for homozygotes.

Type IIb

The high VLDL levels are due to overproduction of substrates, including triglycerides, acetyl-CoA, and an increase in B-100 synthesis. They may also be caused by the decreased clearance of LDL. Prevalence in the population is 10%.

  • Familial combined hyperlipoproteinemia (FCH)
  • Lysosomal acid lipase deficiency, often called (Cholesteryl ester storage disease)
  • Secondary combined hyperlipoproteinemia (usually in the context of metabolic syndrome, for which it is a diagnostic criterion)

Type III

This form is due to high chylomicrons and IDL (intermediate density lipoprotein). Also known as broad beta disease or dysbetalipoproteinemia, the most common cause for this form is the presence of ApoE E2/E2 genotype. It is due to cholesterol-rich VLDL (β-VLDL). Its prevalence has been estimated to be approximately 1 in 10,000.[15]

It is associated with hypercholesterolemia (typically 8–12 mmol/L), hypertriglyceridemia (typically 5–20 mmol/L), a normal ApoB concentration, and two types of skin signs (palmar xanthomata or orange discoloration of skin creases, and tuberoeruptive xanthomata on the elbows and knees). It is characterized by the early onset of cardiovascular disease and peripheral vascular disease. Remnant hyperlipidemia occurs as a result of abnormal function of the ApoE receptor, which is normally required for clearance of chylomicron remnants and IDL from the circulation. The receptor defect causes levels of chylomicron remnants and IDL to be higher than normal in the bloodstream. The receptor defect is an autosomal recessive mutation or polymorphism.

Type IV

Familial hypertriglyceridemia is an autosomal dominant condition occurring in approximately 1% of the population.[rx] This form is due to a high triglyceride levels. Other lipoprotein levels are normal or increased a little. Treatment includes diet control, fibrates, and niacin. Statins are not better than fibrates when lowering triglyceride levels.

Type V

Hyperlipoproteinemia type V, also known as mixed hyperlipoproteinemia familial or mixed hyperlipidemia,[rx] is very similar to type I, but with high VLDL in addition to chylomicrons.

It is also associated with glucose intolerance and hyperuricemia.

In medicine, combined hyperlipidemia (or -aemia) (also known as “multiple-type hyperlipoproteinemia”) is a commonly occurring form of hypercholesterolemia (elevated cholesterol levels) characterized by increased LDL and triglyceride concentrations, often accompanied by decreased HDL.[rx] On lipoprotein electrophoresis (a test now rarely performed) it shows as a hyperlipoproteinemia type IIB. It is the most common inherited lipid disorder, occurring in about one in 200 persons. In fact, almost one in five individuals who develop coronary heart disease before the age of 60 has this disorder. The elevated triglyceride levels (>5 mmol/l) are generally due to an increase in very low density lipoprotein (VLDL), a class of lipoprotein prone to cause atherosclerosis.

Others Types

  • Familial combined hyperlipidemia (FCH) is the familial occurrence of this disorder, probably caused by decreased LDL receptor and increased ApoB.
  • FCH is extremely common in people who suffer from other diseases from the metabolic syndrome (“syndrome X”, incorporating diabetes mellitus type II, hypertension, central obesity and CH). Excessive free fatty acid production by various tissues leads to increased VLDL synthesis by the liver. Initially, most VLDL is converted into LDL until this mechanism is saturated, after which VLDL levels elevate.

Both conditions are treated with fibrate drugs, which act on the peroxisome proliferator-activated receptors (PPARs), specifically PPARα, to decrease free fatty acid production. Statin drugs, especially the synthetic statins (atorvastatin and rosuvastatin) can decrease LDL levels by increasing hepatic reuptake of LDL due to increased LDL-receptor expression.

Unclassified familial forms

These unclassified forms are extremely rare:

  • Hyperalphalipoproteinemia
  • Polygenic hypercholesterolemia

Acquired (secondary)

Acquired hyperlipidemias (also called secondary dyslipoproteinemias) often mimic primary forms of hyperlipidemia and can have similar consequences.[rx] They may result in increased risk of premature atherosclerosis or, when associated with marked hypertriglyceridemia, may lead to pancreatitis and other complications of the chylomicronemia syndrome.[rx] The most common causes of acquired hyperlipidemia are:

  • Diabetes mellitus[rx]
  • Use of drugs such as thiazide diuretics, beta-blockers, and estrogens

Other conditions leading to acquired hyperlipidemia include:

  • Hypothyroidism
  • Kidney failure
  • Nephrotic syndrom
  • Alcohol consumption[rx]
  • Some rare endocrine disorders[rx] and metabolic disorders[rx]

Treatment of the underlying condition, when possible, or discontinuation of the offending drugs usually leads to an improvement in hyperlipidemia. Another acquired cause of hyperlipidemia, although not always included in this category, is postprandial hyperlipidemia, a normal increase following ingestion of food.[rx][rx]

Causes of Hyperlipidemia

Hyperlipidemia subdivides into two broad classifications: primary (familial) or secondary (acquired) hyperlipidemia. Primary hyperlipidemia derives from a plethora of genetic disorders that a patient may inherit through birth, while secondary hyperlipidemia typically originates from an alternate underlying etiology, such as an unhealthy diet, medications (amiodarone, glucocorticoids), hypothyroidism, uncontrolled diabetes, and/or a poor lifestyle regimen.

Underlying disturbances in lipoprotein metabolism are often familial, making a patient’s family history that much more valuable. For example, about 54 percent of patients (in one study) with a history of premature coronary artery disease had an underlying hereditary disorder. In most patients, hyperlipidemia has a polygenic inheritance pattern, and manifestations of the disorder are largely influenced by secondary factors such as (central) obesity, saturated fat intake, and the cholesterol content within a person’s diet. Various less conventional risk factors will also appear below.

Cholesterol is the circulating fatty substance, most implicated in the atherogenic process. Its origin is twofold: 300 to 700 mg per day is of exogenous origin, that is, coming from an excessive intake of dietary fats, especially of animal origin; 800 to 1200 mg per day is the work of an endogenous synthesis, in particular the liver. In addition to excessive consumption of animal fats, other frequent causes of hypercholesterolemia and/or increase in triglycerides are diabetes, chronic renal failure, nephrotic syndrome, hypothyroidism, age, sedentary lifestyle. Other iatrogenic causes may be the intake of certain drugs such as thiazide diuretics, beta-blockers, estrogen-progestin contraceptives, antiretrovirals.

Genetic dyslipidaemias, much rarer, are the basis of the changes in the blood lipid rate in the measure of about 60% and are often responsible for cardiovascular diseases at an early age.

Genetic causes of hyperlipidemia [

Isolated cholesterol elevation
Genetic Familial Hypercholesterolemia relatively common (1 in 500 heterozygotes); TC exceeds 300 mg/dL, family history of elevated TC common, associated with tendon xanthomas, premature (20 – 40 years old) CVD is common Homozygotes are rare but have TC > 600 and if not treated usually die of MI prior to age 20.
Familial Defective Apolipoprotein B100 increases LDL and has a phenotype that is indistinguishable from that of FH, including increased susceptibility to CHD
Mutations Associated with Elevated LDL Levels Rare and isolated; suspect if elevated LDL unresponsive to treatment
Elevated Plasma Lipoprotein(a) Relationship to CVD unclear studies contradictory [;
Polygenic Hypercholesterolemia No family history, no physical manifestations such as xanthomas, the exact cause is unknown
Lp(X) Associate with obstructive hepatic disease, CVD risk unclear
Sitosterolemia rare; plant sterols absorbed in large amounts, tendon xanthomas develop in childhood, LDL levels normal to high
Cerebrotendinous Xanthomatosis rare; associated with neurologic disease, tendon xanthomas, and cataracts in young adults
Elevated cholesterol and triglycerides
Combined (Familial) Hyperlipidemia May occur randomly or with a strong family history of hyperlipidemia; type 2 diabetes and metabolic syndrome are associated and can make diagnosis more difficult
Familial Dysbetalipoproteinemia (Type III Hyperlipoproteinemia) severe hypertriglyceridemia and hypercholesterolemia (both often > 300), associated with premature diffuse vascular disease, male predominance, Palmar xanthomas are pathognomonic
Hepatic Lipase Deficiency Rare disorder with very high cholesterol and triglyceride concentrations, phenotypically similar to familial dysbetalipoproteinemia.
Isolated triglyceride elevations
LPL deficiency Results in elevated chylomicrons, which carry dietary fat; chylomicrons are generally not present after an overnight fast, so a creamy looking plasma in a fasting specimen should be a clue to the diagnosis, especially if seen in young children; extremely high triglycerides can lead to pancreatitis
ApoCII deficiency This apolipoprotein is an activator of LPL; its absence causes a clinical picture identical to LPL deficiency
Familial hypertriglyceridemia Autosomal dominant inheritance; the Main defect is an overproduction of VLDL triglycerides by the liver;
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Secondary causes of hyperlipidemia

Diet Drugs Disease &
Disorders of
Saturated & trans Fats Thiazide Diuretics Hypothyroidism
Excess Calories Beta-Blockers Obesity
Alcohol Glucocorticoids Type 2 Diabetes
Red meat Sex hormones Metabolic syndrome
Whole milk Retinoic Acid derivations Renal disease
High sugar beverages & foods Antipsychotics HIV
Antiretrovirals PCOS
Immunosuppressive agents

Diagnosis of Hyperlipidemia


In the presence of hyperlipidemia, not only the vascular structures are negatively involved but also other tissues. Fort example, research has demonstrated through patellar tendon shear wave velocities that there is a direct relationship between the intrinsic alteration of the patellar tendon and the presence of hyperlipidemia. The tendon becomes stiffer with morphological alteration of the tissue and changes in the type of cells present. Increases the number of macrophages in the tendon tissue, damaged collagen fibers, replacement of collagen cells with lipid cells; collagen type III increases, which is less elastic, matrix metalloproteinases increase. The tendon in the presence of hyperlipidemia becomes mechanically less effective and more prone to injury.


Content Strength of recommendation Level of evidence
1 Patients with CVD (CAD, peripheral artery disease, atherosclerotic ischemic stroke, transient ischemic attack) are classified as a very high-risk group, and the treatment goal is to lower LDL-C levels to < 70 mg/dL or by > 50% from the baseline level for secondary prevention. I A
2 If acute myocardial infarction occurs, administer statins immediately regardless of the baseline LDL-C level. I A
3 Patients with carotid disease (significant carotid artery stenosis), abdominal aortic aneurysm, or diabetes are classified as a high-risk group. For this group, begin treatment when LDL-C concentration is ≥ 100 mg/dL for primary prevention. I A
4 Patients with two or more major risk factors other than LDL-C are classified as a moderaterisk group. For this group, administer statin if LDL-C concentration is ≥ 130 mg/dL even after weeks or months of lifestyle adjustment. II B
5 Patients with one or fewer major risk factors other than LDL-C are classified as low-risk group. For this group, administer statin if LDL-C concentration ≥ 160 mg/dL even after weeks or months of lifestyle adjustment. II B
6 If LDL-C concentration is ≥ 190 mg/dL, check whether the patient has other causes for hyperlipidemia, such as biliary obstruction, nephrotic syndrome, hypothyroidism, pregnancy, use of glucocorticoids or cyclosporine and make necessary adjustments. I B
7 If LDL-C concentration is ≥ 190 mg/dL in absence of secondary causes, begin statin administration regardless of the risk. I A
8 If blood triglyceride concentration rises to ≥ 500 mg/dL, check for secondary causes of triglyceride elevation, such as weight gain, drinking, carbohydrate intake, chronic kidney disease, diabetes, hypothyroidism, pregnancy, and use of estrogen, tamoxifen, or glucocorticoids and for other genetic problems that may cause abnormal lipid metabolism. I A
9 If triglyceride concentration is consistently ≥ 500 mg/dL, drug therapy, such as fibrate and omega-3 fatty acid therapy, may be initiated to prevent pancreatitis. II A
10 If triglyceride concentration is between 200–499 mg/dL with high LDL-C level, it is recommended to begin statin administration to primarily lower LDL-C concentration to the targeted level. I A
11 If hypertriglyceridemia persists (≥ 200 mg/dL) even after lifestyle adjustment and statin administration in very highrisk and high-risk patients, drugs that lower triglyceride levels, such as fibrate or omega-3 fatty acids, may be additionally used to prevent CVD. II B

Exams and Tests

A cholesterol test is done to diagnose a lipid disorder. Different experts recommend different starting ages for adults.

  • Recommended starting ages are between 20 to 35 for men and 20 to 45 for women.
  • Adults with normal cholesterol levels do not need to have the test repeated for 5 years.
  • Repeat testing sooner if changes occur in lifestyle (including weight gain and diet).
  • Adults with a history of elevated cholesterol, diabetes, kidney problems, heart disease, and other conditions require more frequent testing.

It is important to work with your health care provider to set your cholesterol goals. Newer guidelines steer doctors away from targeting specific levels of cholesterol. Instead, they recommend different medicines and doses depending on a person’s history and risk factor profile. These guidelines change from time to time as more information from research studies becomes available.

General targets are:

  • LDL: 70 to 130 mg/dL (lower numbers are better)
  • HDL: More than 50 mg/dL (higher numbers are better)
  • Total cholesterol: Less than 200 mg/dL (lower numbers are better)
  • Triglycerides: 10 to 150 mg/dL (lower numbers are better)

If your cholesterol results are abnormal, you may also have other tests such as:

  • Blood sugar (glucose) test to look for diabetes
  • Kidney function tests
  • Thyroid function tests to look for an underactive thyroid gland

History and Physical

Regularly, patients presenting with underlying hyperlipidemia remain asymptomatic, therefore obtaining a precise and thorough history is essential. Upon taking a patients history, it is crucial to obtain a profound understanding of each patient’s family history of cardiovascular disease, hyperlipidemia, and/or familial hypercholesterolemia; their diet and exercise habits; tobacco, alcohol, or drug use; the presence of coronary artery disease; risk factors or history of CAD; and/or symptoms of peripheral arterial disease or angina

In addition to obtaining a detailed history, a focused physical exam is also very important. Obtaining accurate blood pressure measurements, observing the patients skin for xanthomas, listening for carotid and femoral bruits for evidence of stenosis, listening for an S4 heart sound, and palpating for intact peripheral pulses in all four extremities are fast and simple physical exam findings that can assist in your diagnosis of hyperlipidemia


Various experts have developed lipid screening guidelines that include the “lipid profile” to measure cholesterol and triglyceride levels. Guidelines differ as to what age primary providers should start screening and how often they should screen patients for hyperlipidemia. In general, it is advised that routine lipid screening should occur when a male turns 35 years of age (if no other cardiovascular risk factors) or 25 years of age (if the patient has other cardiovascular risk factors). It is also suggested that routine lipid screening be initiated in females at 45 years of age (if no other cardiovascular risk factors present) or 30 to 35 years of age (if the patient has other cardiovascular risk factors) For lower-risk patients, lipid screening every five years is reasonable, and more frequent screening is recommended as the patient’s cardiovascular risk increases.

As stated above, the most valuable laboratory test to collect is checking fasting lipid profile, which routinely includes LDL, HDL, triglycerides, and total cholesterol. A v-LDL, total cholesterol: HDL, and LDL: HDL ratios can be added on for a more comprehensive test. It is necessary to not eat or drink anything besides water for 9 to 12 hours as not to skew the results of the lipid panel (mainly the triglyceride levels).

Before starting a statin for high LDL levels, it is important to obtain liver function tests to ensure there is no prior liver dysfunction, as statins may exacerbate this issue. For risk stratification purposes, a Hgb A1c level is necessary to screen for diabetes mellitus, and the clinician should always examine blood pressure measurements to ensure the patient does not have underlying hypertension. Additionally, a TSH should be ordered to rule out underlying thyroid abnormalities, and a simple urinalysis can be collected to screen for albuminuria. These tests are critical for risk-stratification of your patient to accurately assess the potential risks versus benefits of initiating medical therapy in a patient with hyperlipidemia.

Treatment of Hyperlipidemia

The decision to treat elevated LDL cholesterol levels depends on the determination of overall cardiovascular risk by the patient’s primary physician, and this should be discussed in great detail with the patient. The absolute risk reduction affiliated with lipid-lowering therapy for hyperlipidemia is generally less than for patients with known underlying cardiovascular disease. To reduce risk in patients without a known diagnosis of cardiovascular disease, only treatments of elevated LDL cholesterol have proven to be of clinical benefit. There is no proven clinical benefit to the treatment of hypertriglyceridemia or low HDL cholesterol levels.

Initial treatment modalities are focused on diet and lifestyle modification, with the possible addition of lipid-lowering medications if needed. Patients with mild hyperlipidemia and low ASCVD risk (below 7.5% 10-year risk) should focus on a low fat, low carbohydrate diet, and moderate to high-intensity physical activity (recommended 30 minutes per day, 5 to 6 days per week). The AHA advises limiting saturated fat consumption to about 5% of your daily calories and restricting the total quantity of trans-saturated fat consumption as much as possible. Quitting smoking, lowering blood pressure, and losing weight have all proven to be very advantageous in regards to lowering vascular disease risk. For patients at moderate to high ASCVD risk (over 7.5% 10-year risk), the addition of lipid-lowering “statin” medications should be added.

The most well rounded and complete meta-analysis investigating primary prevention trials in hyperlipidemia patients discovered an all-cause mortality benefit and that lowering LDL cholesterol is effective at decreasing cardiovascular events, in particular, reducing the risk of myocardial infarction. There is a clear and proven benefit to statin therapy for the vast majority of patients, from low risk to high risk, and if side effects and financial constraints did not exist, almost all patients would be prescribed statin therapy. Therefore, these medication’s side effects and costs should be weighed against the individual patient’s potential benefit from taking the drug.

Key Recommendations for Practice: SORT evidence rating system :

  • Patients with a high risk of ASCVD (>7.5% 10-year risk) should receive statin therapy for primary prevention: Rating B.
  • Statin therapy should be initiated for secondary prevention in patients with known ASCVD, absent any contraindication: Rating A
  • Niacin, fibrates, and omega-3 fatty acids should not be routinely given for primary or secondary prevention of ASCVD: Rating A
  • A moderate-intensity statin plus ezetimibe should merit consideration as an alternative in patients with acute coronary syndrome who cannot tolerate high-intensity statin therapy: Rating B.
  • Moderate-intensity statins include: lovastatin 40 mg, pravastatin 40 mg, simvastatin 40 mg, atorvastatin 10 to 20 mg, and rosuvastatin 5 to 10 mg
  • High-intensity statins include: atorvastatin 40 to 80 mg, rosuvastatin 20 to 40 mg

If the provider and patient reach a mutual decision to initiate medical therapy with statins, the overall risk reduction in cardiovascular events is customarily around 20 to 30% in most clinical trials. The commonly referred to trials of which the majority of guidelines are based, included pravastatin 40 mg, lovastatin 20 to 40 mg, atorvastatin 10 mg, and rosuvastatin 10 mg, so general recommendations are to choose one of these statins listed. It is always important to schedule close follow up with patients that are starting lipid-lowering statin therapy. The vast majority of benefits arising from statin therapy originates from the moderate dose, with a much more diminutive benefit deriving from the addition of high-intensity therapy. However, the benefit of high-intensity therapy remains clinically significant and should merit consideration for all high-risk patients.

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If a patient encounters an allergy or intolerance to a statin medication, the suggestion is to reduce the original or to transition to a different lipid-lowering medication altogether. Among patients that have reported muscle-related statin intolerances, according to one 24 week trial, evolocumab (PCSK9 inhibitor) reduced LDL cholesterol levels significantly more when compared to ezetimibe. However, both of these medications are reasonable secondary options for treatment.

Current HMG-CoA-inhibitors.

Drug Trade
% TG
Fluvastatin Lescol 20–80 mg 22–35 3–11 17–21
Pravastatin Pravachol 10–80 mg 22–37 2–12 15–24
Lovastatin Altoprev/Mevacor 10–80 mg 21–42 2–8 6–21
Simvastatin Zocor 5–80 mg 26–47 10–16 12–33
Atorvastatin Lipitor 10–80 mg 39–60 5–9 19–37
Rosuvastatin Crestor 5–40 mg 45–63 8–10 10–30
Pitavastatin Livalo 1–4 mg 38–44 5–8 14–22

Statin alternatives

Bile acid sequestrants
Cholestyramine (4–16 g)
Colestipol (5–20 g)
Colesevelam (2.6–3.8 g)
LDL    −15–30%
HDL    +3–5%
TG      No change or
of other drugs
Nicotinic acid
Immediate release
(crystalline) nicotinic acid
(1.5–3 gm), extended
release nicotinic acid
(Niaspan®) (1–2 g),
sustained release
nicotinic acid (1–2 g)
LDL    −5–25%
HDL    +15–35%
TG      −20–50%
(or gout)
Upper GI distress
Fibric acids
(600 mg BID)
Fenofibrate (200 mg)
Clofibrate(1000 mg
LDL     −5–20%
(may be increased in
patients with high TG)
HDL   +10–20%
TG      −20–50%
Zetia (10 mg daily)
As monotherapy, often combined with
a statin
LDL-C      −18%
HDL-C      +3%
TG      −8%
Nasopharyngitis or
regarding reduction
of CVD events
Omega 3 fatty acids
Fish Oil
Plant sources
Prescription fatty acid ester indicated only for
treatment of TG > 500 mg/dl to prevent
Fish oil has been shown to reduce elevated TG
with a subsequent mild reduction in LDL and
non-HDL-C; however a recent major study
showed no benefit from fish oil capsules;
consumption of fish is preferred. Plant sources
of omega-3 FA have been subjected to few
clinical trials with CVD endpoints


Statins lower cholesterol levels through three mechanisms linked to each other []. The first is the selective and competitive inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, an enzyme that limits the conversion speed of HMG-CoA to mevalonic acid, a precursor of sterols, including cholesterol. Inhibition of this enzyme initially leads to a reduction in liver cholesterol, but compensatory mechanisms induce greater expression of both HMG-CoA reductase and LDL receptors []. In the latter case, statins, therefore, act with an indirect mechanism, by increasing receptor-mediated absorption of LDL, hence reducing plasma LDL. Thanks to the higher number of receptors, they also reduce VLDL and IDL, which are LDL precursors: this third mechanism of action further contributes to lowering plasma LDL-C. In particular, atorvastatin and rosuvastatin produce a marked decrease in plasma triglycerides (TG), as they remove larger amounts of VLDL rich in triglycerides []. Statins are structural analogs of the HMG-CoA intermediate, which is formed by HMG-CoA reductase in mevalonate synthesis. Only lovastatin and simvastatin are inactive relations, which are hydrolyzed in vivo into the corresponding active β-hydroxy acid form [].


Fibrates (fenofibrate, bezafibrate, ciprofibrate, and gemfibrozil) are a class of lipid-lowering drugs and exert their effects mainly by activating the peroxisome proliferator-activated receptor-alpha (PPAR-alpha), while bezafibrate is an agonist for all three PPAR isoforms (alpha, gamma and delta). Fibrates decrease triglyceride levels and increase HDL-C levels ; the latter effect is more pronounced in patients with hypertriglyceridemia []. The effect on LDL-C levels varies. They may reduce LDL-C levels in patients with low triglycerides, but may paradoxically increase levels for patients with high triglyceride levels [], and significantly reduce the levels of highly atherogenic remnant lipoproteins in a more efficient way than statins.

The recommended dose for adults of Bezafibrate is 200 mg three times a day, or 400 mg of modified-release tablet a day at the main meals []. Fenofibrate can be administered once a day (200 mg) or with four 67 mg capsules, if required. However, there are some fenofibrate formulations using a NanoCrystal technology (48 and 145 mg) that eliminates the requirement of taking the drug with a meal, or micronized capsules (67, 134, and 200 mg) resulting in greater solubility and improved bioavailability []. The Gemfribozil dose range is 900–1200 mg daily.

Bile Acid Sequestrants

Bile acid-binding resins, including cholestyramine, colesevelam, and colestipol, are orally administered anion-exchange resins that are neither absorbed systemically nor metabolized by digestive enzymes. At the intestinal level, therefore, they bind to the two main biliary acids (glycocholic acid and taurocholic acid) making an insoluble complex that is excreted with the faeces  []. This leads to a continuous, though partial, removal of bile acids from the enterohepatic circulation. Consequently, the lower concentration of these in the liver obstructs 7α-hydroxylase feedback inhibition, increasing the hepatic conversion of cholesterol to bile acids. Decreasing concentrations of hepatic cholesterol cause the number of compensatory effects, such as increased plasma LDL and IDL uptake by increasing the number of high-affinity receptors for LDLs present on cell membranes, especially in the liver, and induction of the HMG-CoA reductase enzyme. Despite the fact that resins cause increased hepatic cholesterol synthesis, there is a lowering of cholesterol levels in plasma. The selectivity of these compounds depends on the fact that the resins, positively charged, do not bind to all anions as well. For example, cholestyramine ions can only be displaced by other anions that have an affinity for functional groups positively charged by resins (such as bile acids). Furthermore, resins can affect TGs and induce a 5% of the increase in HDL-C levels [].


Ezetimibe is the first representative of a group of drugs capable of selectively inhibiting the intestinal absorption of phytosterols and dietary cholesterol. Once orally taken, it is located on the small intestine brush lining and inhibits cholesterol absorption, resulting in a decrease in intestinal cholesterol passage to the liver []. The ezetimibe molecular target is a sterol transport , Niemann-Pick C1-Like 1 (NPC1L1), responsible for intestinal cholesterol capture and absorption of phytosterols. Lower cholesterol absorption leads to increased receptor-mediated LDL uptake but, if the drug is used in monotherapy, lower cholesterol absorption may be offset by increased biosynthesis. The molecule appears to be selective because it does not interfere with the absorption of triglycerides, liposoluble vitamins, fatty acids, bile acids, progesterone, and ethinyl estradiol []. The recommended dose for adults is one tablet of ezetimibe 10 mg once daily, while for children the start of treatment should be under the supervision of a specialist [].


Niacin, also called vitamin B3, PP, or nicotinic acid, significantly raises HDL levels while decreasing those of VLDL and LDL with mechanisms that do not involve cholesterol biosynthesis or catabolism. This molecule, in fact, prevents lipolysis in adipose tissue as it is a powerful inhibitor of the intracellular lipase system, generating multiple effects that eventually lead to the reduction of plasma cholesterol and triglycerides []. Reduction of lipolysis decreases FFA mobilization, decreasing their levels in the liver, resulting in a decrease in the hepatic synthesis of triglycerides with consequent lower production of VLDL. A further mechanism of action of niacin consists of the ability of nicotinic acid to stimulate the activity of lipoprotein lipase, thus increasing the clearance of VLDL: the lower quantity of VLDL leads to reduced levels of LDL, which is derived from LDL

Omega-3 Fatty Acids

Omega-3 fatty acids are polyunsaturated fatty acids with a double bond at the third carbon atom from the end of the carbon chain. They become part of the cell membrane, as with other fatty acids, and thanks to their chemical-physical characteristics, they determine the fluidity characteristics of membranes.

Omega-3 has shown to decrease CVD events as monotherapy in secondary prevention []. However, conflicting results are reported. Meta-analyses of omega-3 fatty acids added to optimal statin therapy suggest they give no added benefit []. The mechanisms by which omega-3 polyunsaturated fatty acids exert cardiovascular protective effects are both functional and metabolic: they cause greater fluidity of membranes, improve endothelial function, modulate platelet aggregation, modulate the metabolism of eicosanoids, and stabilize atheromatous lesions []. From a metabolic point of view, omega-3 mainly reduces serum triglycerides through an increase in the oxidation of fatty acids, further decreasing their synthesis and modulating the composition of membrane phospholipids. In addition, omega-3 increases LDL diameter (a characteristic that would therefore reduce its atherogenicity) without reducing its plasma levels [].


Alirocumab is a fully human IgG1 monoclonal antibody that binds with high affinity and specificity to proprotein convertase subtilisin/Kexin type 9 (PCSK9) by inhibiting it. PCSK9 usually binds to low-density lipoprotein receptors (LDLR) on the surface of hepatocytes and is able to promote the degradation of such receptors within the liver []. LDLRs are the main receptor that eliminates circulating LDLs, therefore, the reduction of LDLR levels by PCSK9 results in higher levels of circulating LDL-C. Alirocumab inhibits PCSK9 binding with LDL, thus increasing the number of LDLRs available to eliminate LDLs, thus lowering LDL-C levels. LDLR receptors also bind residues of VLDL rich in triglycerides and intermediate-density lipoproteins (IDL). Therefore, treatment with alirocumab may result in a reduction in these lipoprotein residues, demonstrated by decreases in apolipoprotein B (Apo B), non-high-density lipoprotein cholesterol (non-HDL-C), and triglycerides (TG) [].


Evolocumab is an IgG2 human monoclonal antibody produced in Chinese hamster ovary cells (CHO) by recombinant DNA technology []. Evolocumab selectively binds PCSK9 and prevents its binding with the LDLR. Evolocumab results in a reduction in circulating PCSK9, LDL-C, total cholesterol (TC), ApoB, and non-HDL cholesterol, and an increase in HDL-C and Apo11 in patients with primary hypercholesterolemia and mixed dyslipidemia [,].

Evolocumab is indicated in adult patients with primary hypercholesterolemia (familial heterozygous and non-familial) or mixed dyslipidemia, in addition dietary changes. It can be used in combination with a statin, with statins and other hypolipidemic therapies in patients who do not reach target levels of LDL-C with a maximum tolerated statin dose, or in monotherapy or in combination with other hypolipidemic therapies in statin-intolerant patients or patients for whom the use of statins is contraindicated [].


Lomitapide represents a new therapeutic approach for patients with homozygous FH who, despite the widespread use of statins, do not reach LDL targets. It is not authorized for heterozygous FH. It is a selective inhibitor of the microsomal transport protein of triglycerides (MTP), an intracellular protein found in the endoplasmic reticulum of liver and intestine cells which plays a role in the assembly of fats, such as cholesterol and triglycerides, in lipoproteins, and their subsequent release into the blood. The inhibition of MTP reduces the production of chylomicrons in enterocytes and increases the production of very-low-density lipoprotein (VLDL) cholesterol in hepatocytes independently of the LDL receptor  [].


Mipomersen is an antisense oligonucleotide that inhibits the production of about-100 by binding to the mRNA that encodes the synthesis of apoB, an essential component of VLDL and LDL []. Mipomersen reduces the liver levels of mRNA for apoB-100 in a dose-dependent manner, followed by a reduction in LDL-C, LDL, TG, and lipoprotein(a).

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Mipomersen’s half-life is approximately two to five hours, and it has an elimination half-life of one to two months []. It is more than 90% protein-bound and it is metabolized by tissue endonucleases. The estimated subcutaneous bioavailability of mipomersen is between 54% and 78% after a once-weekly dose of 50 to 400 mg [].

The lipid-lowering effects of mipomersen in two-phase three clinical trials have been shown after failed courses of standard lipid-lowering therapy [].

The list of foods to be recommended and to be avoided

Food group Choose these foods, but be careful not to eat excessive Be careful not to eat too much of these foods and eat them too frequently!
Fish/beans/eggs Fish Ground meat, ribs, internal organs of meats
Bean, tofu Poultry skin, fried chicken
Lean meat High-fat processed meat products
Poultry without skin
Dairies Skim milk, powdered skim milk, low fat milk and their products Condensed milk and its products
Cheese, cream cheese
Low-fat cheese Ice cream
Coffee cream
Fats and oils Unsaturated fatty acid: corn oil, olive oil, Butter, pork oil, shortening, bacon oil, beef oil
perilla oil, soybean oil, sunflower oil Cheese- or whole milk-based salad dressing
Low-fat/non-fat salad dressing Hard margarine
Grains Whole grains Butter and margarine-based bread and cake
High-fat crackers, biscuits, chips, butter popcorns
Pastry, cake, donut, high-fat snack
Soup Soup with fat removed after cooking Oily soup, cream soup
Vegetables/fruits Fresh vegetables, seaweeds, fruits Fried or butter-, cheese-, cream-, or sauce-added vegetables/fruits
Sweetened processed products (e.g., canned fruit)
Others Nuts: peanut, walnut Chocolate/sweets
Products with coconut oil or palm oil
Fried snacks

Example of a daily meal plan

Food group Recommendation Serving size of typical foods
Grains Whole grain-based diet Rice (e.g., multigrain rice, brown rice): 210 g (1 bowl)
2/3 to 1 serving every meal Bread (e.g., whole-wheat bread, barley bread): 105 g (3 slices)
Vegetables Diverse types of vegetables Vegetables: 70 g (cooked 1/3 cup)
2.5 to 3 servings every meal Seaweeds: 30 g (cooked 1/5cup)
Fish meat Fish, lean meat, eggs, tofu Fish: 60 g (1 piece of medium-size fish)
1 to 2 servings every meal Lean meat: 60 g (1.5 ping-pong ball size)
Eat blue-backed fish 2 to 3 times a week Eggs: 60 g (1 medium-sized egg)
Tofu: 80 g (1/5 block)
Fruits Fresh fruit 1 serving: 100 g (1/2 of medium-sized apple)

Effect of Weight Loss Drugs

There are several weight loss drugs currently approved for the long-term treatment of obesity. For a detailed discussion of weight loss drugs see the chapter on “Pharmacologic Treatment of Overweight and Obese Adults” [. Weight loss drugs tend to decrease triglyceride and LDL-C levels and increase HDL-C levels due to their ability to decrease weight but the results vary in individual patients.

Orlistat (Xenical)

Orlistat is a lipase inhibitor that decreases fat absorption. Total cholesterol and LDL-C levels decrease with orlistat treatment to a greater degree than expected with diet alone [. For example, in the XENDOS study LDL-C decreased by 12.8% in the orlistat group vs. 5.1% in the placebo group [. Additionally, studies have shown that the levels of small dense LDL are reduced and the average LDL particle size increased with orlistat treatment [. It has been shown that orlistat, in addition to reducing dietary triglyceride absorption, also decreases cholesterol absorption [. A likely mechanism for the decrease in cholesterol absorption is orlistat inhibition of NPC1L1, a transporter in the intestine that mediates cholesterol absorption [. Despite the effect on triglyceride absorption, orlistat does not markedly affect either triglyceride or HDL-C levels beyond what one would expect with weight loss[,

Phenteramine + Topiramate (Qsymia)

Phenteramine is a sympathomimetic amine that induces satiety and topiramate is a neurostabilizer that also decreases appetite. In randomized controlled trials, phentermine + topiramate combination therapy decreased triglyceride levels and increased HDL-C without a consistent effect on LDL-C levels [. It is likely that these changes primarily represent the effect of the weight loss induced by this drug.

Lorcaserin (Belviq)

Lorcaserin is a serotonin 2C receptor agonist that suppresses appetite and induces weight loss. In randomized controlled trials, lorcaserin modestly decreased triglyceride levels and increased HDL-C levels with no effect on LDL-C levels [. Similar to phenteramine + topiramate combination therapy, it is likely that the changes induced by lorcaserin treatment primarily represent the effect of the weight loss induced by this drug. Note that lorcaserin has been withdrawn from the market due to an increased risk of cancer.

Naltrexone + Bupropion (Contrave)

Naltrexone is an opioid antagonist and bupropion is an antidepressant. In large randomized control trials naltrexone + bupropion decreased triglyceride levels by approx. 8-12%, decreased LDL-C levels by 0-6%, and increased HDL-C by 3-8% [. The magnitude of these changes in lipid levels mimics what one would expect from weight loss.

Liraglutide (Saxenda)

Liraglutide is a GLP-1 agonist that has been approved for the treatment of obesity. A large randomized trial demonstrated modest reductions in triglycerides (9%) and LDL-C levels (2.4%) and increases in HDL-C (1.9%) with liraglutide treatment [. Another randomized trial failed to demonstrate changes in lipid parameters [. However, a trial in patients with diabetes also resulted in modest improvements in triglyceride and HDL-C levels [. Thus, liraglutide induces modest changes in the lipid profile that mimics what one observes with weight loss.

How to treat and manage hyperlipidemia at home

Lifestyle changes are the key to managing hyperlipidemia at home. Even if your hyperlipidemia is inherited (familial combined hyperlipidemia), lifestyle changes are still an essential part of treatment. These changes alone may be enough to reduce your risk of complications like heart disease and stroke. If you’re already taking medications, lifestyle changes can improve their cholesterol-lowering effects.

Eat a heart-healthy diet

Making changes to your diet can lower your “bad” cholesterol levels and increase your “good” cholesterol levels. Here are a few changes you can make:

  • Choose healthy fats. Avoid saturated fats that are found primarily in red meat, bacon, sausage, and full-fat dairy products. Choose lean proteins like chicken, turkey, and fish when possible. Switch to low-fat or fat-free dairy. And use monounsaturated fats like olive and canola oil for cooking.
  • Cut out the trans fats. Trans fats are found in fried food and processed foods, like cookies, crackers, and other snacks. Check the ingredients on product labels. Skip any product that lists “partially hydrogenated oil.”
  • Eat more omega-3s. Omega-3 fatty acids have many heart benefits. You can find them in some types of fish, including salmon, mackerel, and herring. They can also be found in some nuts and seeds, like walnuts and flax seeds.
  • Increase your fiber intake. All fiber is heart-healthy, but soluble fiber, which is found in oats, brain, fruits, beans, and vegetables, can lower your LDL cholesterol levels.
  • Learn heart-healthy recipes. Check out the American Heart Association’s recipe page for tips on delicious meals, snacks, and desserts that won’t raise your cholesterol.
  • Eat more fruits and veggies. They’re high in fiber and vitamins and low in saturated fat.

Lose weight

If you’re overweight or obese, losing weight can help lower your total cholesterol levels. Even 5 to 10 pounds can make a difference.

Losing weight starts with figuring out how many calories you’re taking in and how many you’re burning. It takes cutting 3,500 calories from your diet to lose a pound.

To lose weight, adopt a low-calorie diet and increase your physical activity so that you’re burning more calories than you’re eating. It helps to cut out sugary drinks and alcohol, and practice portion control.

Get active

Physical activity is important for overall health, weight loss, and cholesterol levels. When you aren’t getting enough physical activity, your HDL cholesterol levels go down. This means there isn’t enough “good” cholesterol to carry the “bad” cholesterol away from your arteries.

You only need 40 minutes of moderate to vigorous exercise three or four times a week to lower your total cholesterol levels. The goal should be 150 minutes of exercise total each week. Any of the following can help you add exercise to your daily routine:

  • Try biking to work.
  • Take brisk walks with your dog.
  • Swim laps at the local pool.
  • Join a gym.
  • Take the stairs instead of the elevator.
  • If you use public transportation, get off a stop or two sooner.

Quit smoking

Smoking lowersTrusted Source your “good” cholesterol levels and raises your triglycerides. Even if you haven’t been diagnosed with hyperlipidemia, smoking can increase your risk of heart disease. Talk to your doctor about quitting or try the nicotine patch. Nicotine patches are available at the pharmacy without a prescription.

Interpreting the numbers

In the United States, cholesterol levels are measured in milligrams (mg) of cholesterol per deciliter (dL) of blood. In Canada and many European countries, cholesterol levels are measured in millimoles per liter (mmol/L). To interpret your test results, use these general guidelines.

Total cholesterol (U.S. and some other countries) Total cholesterol* (Canada and most of Europe) Results
*Canadian and European guidelines differ slightly from U.S. guidelines. These conversions are based on U.S. guidelines.
Below 200 mg/dL Below 5.2 mmol/L Desirable
200-239 mg/dL 5.2-6.2 mmol/L Borderline high
240 mg/dL and above Above 6.2 mmol/L High
LDL cholesterol (U.S. and some other countries) LDL cholesterol* (Canada and most of Europe) Results
*Canadian and European guidelines differ slightly from U.S. guidelines. These conversions are based on U.S. guidelines.
Below 70 mg/dL Below 1.8 mmol/L Best for people who have heart disease or diabetes.
Below 100 mg/dL Below 2.6 mmol/L Optimal for people at risk of heart disease.
100-129 mg/dL 2.6-3.3 mmol/L Near optimal if there is no heart disease. High if there is heart disease.
130-159 mg/dL 3.4-4.1 mmol/L Borderline high if there is no heart disease. High if there is heart disease.
160-189 mg/dL 4.1-4.9 mmol/L High if there is no heart disease. Very high if there is heart disease.
190 mg/dL and above Above 4.9 mmol/L Very high
HDL cholesterol(U.S. and some other countries) HDL cholesterol*(Canada and most of Europe)
Below 40 mg/dL, menBelow 50 mg/dL, women Below 1 mmol/LBelow 1.3 mmol/L Poor
40-59 mg/dL, men50-59 mg.dL, women 1-1.5 mmol/L1.3-1.5 mmol/L Better
60 mg/dL and above Above 1.5 mmol/L Best



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